Advanced Prostate Cancer Drug May Help at Earlier Stage

In continuation of my update on abiraterone

Advanced Prostate Cancer Drug May Help at Earlier Stage:  A drug approved to treat advanced prostate cancer appears to help men who have localized high-risk prostate cancer if given before surgery. Adding Zytiga (abiraterone) to conventional hormonal treatments eliminated or nearly...

Experimental Drug Helps Fight Some Childhood Cancers, Study Finds

In continuation of my update on Crizotinib

Experimental Drug Helps Fight Some Childhood Cancers, Study Finds:  A new targeted drug therapy may help treat certain advanced cancers in children, a new preliminary study indicates.In some cases, the oral medication even made tumors disappear after regular cancer treatments had failed, the...

Abiraterone acetate can help eliminate prostate tumors

In continuation of my update Abiraterone

Abiraterone acetate can help eliminate prostate tumors: A hormone-depleting drug approved last year for the treatment of metastatic prostate cancer can help eliminate or nearly eliminate tumors in many patients with aggressive cancers that have yet to spread beyond the prostate, according to a clinical study to be presented at the annual meeting of the American Society of Clinical Oncology (ASCO), June 1-5, in Chicago.

Mylan receives final FDA approval for Clopidogrel Tablets ANDA

Mylan receives final FDA approval for Clopidogrel Tablets ANDA: Mylan Inc.  announced that its subsidiary Mylan Pharmaceuticals Inc. has received final approval from the U.S. Food and Drug Administration (FDA) for its Abbreviated New Drug Application (ANDA) for Clopidogrel Tablets USP, 75 mg and 300 mg.

Celery Chemical, Apigenin Tackles Breast Cancer

Apigenin, a natural substance found in grocery store produce aisles, shows promise as a non-toxic treatment for an aggressive form of human breast cancer, following a new study at the University of Missouri. MU researchers found apigenin shrank a type of breast cancer tumor that is stimulated by progestin, a synthetic hormone given to women in combination with estrogens to ease symptoms related to menopause.

“This is the first study to show that apigenin, which can be extracted from celery, parsley and many other natural sources, is effective against human breast cancer cells that had been influenced by a certain chemical used in hormone replacement therapy,” said co-author Salman Hyder, the Zalk Endowed Professor in Tumor Angiogenesis and professor of biomedical sciences in the College of Veterinary Medicine and the Dalton Cardiovascular Research Center.

In the study, Hyder and his colleagues implanted cells of a deadly, fast-growing human breast cancer, known as BT-474, into a specialized breed of mouse. Some of the mice were then treated with medroxyprogesterone acetate (MPA), a type of progestin commonly given to post-menopausal women. A control group did not receive MPA.

Later one group of MPA-treated mice was treated with apigenin. Cancerous tumors grew rapidly in the mice which did not receive apigenin. In the apigenin-treated mice, breast cancer cell growth dropped to that of the control group, and the tumors shrank.

New combination of two previously approved FDA drugs treat lung cancer

In continuation of my update on Erlotinib..

Dr. Narla's laboratory focuses on the identification and characterization of the genes and pathways involved in cancer metastasis. By studying the functional role of the KLF6 tumor suppressor gene, Dr. Narla and his team have identified new signaling pathways regulated by this gene family thus providing new insight into cancer diagnosis and treatment. The team's research found that KLF6 and FOXO1, both tumor suppressor genes, are turned off as cancer spreads through the body. By using a combination of two existing FDA drugs -Erlotinib (left structure), a targeted cancer drug, and Trifluoperazine (below right structure), a medication used to treat schizophrenia, the team developed an understanding of the properties that turn these critical genes back on, initiating tumor cells to die.

Since first discovering the KLF6 gene 13 years ago as a medical student at the Mount Sinai School of Medicine in the laboratory of Dr. Scott Friedman, Dr. Narla has been involved in the identification and characterization of the KLF6 gene and its role in cancer development and the progression of cancer.

Read details at JCI.....

New combination of two previously approved FDA drugs treat lung cancer

Caffeine can prevent memory loss in diabetes

Caffeine can prevent memory loss in diabetes: Badly controlled diabetes are known to affect the brain causing memory and learning problems and even increased incidence of dementia, although how this occurs is not clear. But now a study in mice with type 2 diabetes has discovered how diabetes affects a brain area called hippocampus causing memory loss, and also how caffeine can prevent this. 

Isis commences ISIS-APOCIIIRx Phase 2 study in hypertriglyceridemia

Isis commences ISIS-APOCIIIRx Phase 2 study in hypertriglyceridemia: 

Isis Pharmaceuticals, Inc. announced the initiation of a Phase 2 study 

evaluating ISIS-APOCIIIRx in patients with hypertriglyceridemia......

Ref:http://ir.isispharm.com/phoenix.zhtml?c=222170&p=irol-newsArticle_pf&ID=1509616

Potential new drugs for fox tapeworm infection in humans

Potential new drugs for fox tapeworm infection in humans: Scientists are reporting development and testing of a new series of drugs that could finally stop the fox tapeworm  which causes a rare but life-threatening disease in humans  dead in its tracks. The report shows that specific organometallic substances that help combat cancer are also the surprising best new hope for a treatment against tapeworm infection.

The group prepared and evaluated several ruthenium complexes (see structure)

as potential drugs against the fox tapeworm. Some were effective in killing the tapeworms and also were less toxic on normal cells in laboratory dish tests, making them prime candidates for further development as treatments for AE.

Ref : http://pubs.acs.org/doi/full/10.1021/jm300291a#showFigures
        http://pubs.acs.org/doi/suppl/10.1021/jm300291a/suppl_file/jm300291a_si_001.pdf

Phase I clinical trial shows drug shrinks melanoma brain metastases

The drug dabrafenib (see structure), which targets the Val600 BRAF mutation that is active in half of melanoma cases, also cut the size of tumors in 25 of 36 patients with late-stage melanoma that had not spread to the brain. The drug also showed activity in other cancer types with the BRAF mutation.

"Nine out of 10 responses among patients with brain metastases is really exciting. No other systemic therapy has ever demonstrated this much activity against melanoma brain metastases," said study co-lead author Gerald Falchook, M.D., assistant professor in the Department of Investigational Cancer Therapeutics at The University of Texas MD Anderson Cancer Center.

Phase I clinical trial shows drug shrinks melanoma brain metastases

Scientists Discover Drug Candidate for Alzheimer’s, Huntington’s

Scientists at the Gladstone Institutes have identified a drug candidate that diminishes the effects of both Alzheimer's disease and Huntington's disease in animal models, offering new hope for patients who currently lack any medications to halt the progression of these two debilitating illnesses.

Gladstone Investigator Paul Muchowski, PhD, has identified a new compound called JM6 in experiments done in collaboration with an international team of researchers, and which are being published today in an online article in Cell. In laboratory tests involving mice genetically engineered to model one or the other of the two diseases, Dr. Muchowski's team found that JM6 blocks kynurenine 3-monooxygenase (KMO), an enzyme that has long been speculated to play a role in neurodegenerative diseases.

In mice modeling Alzheimer's disease, the novel compound prevented memory deficits and the loss of synaptic connections between brain cells—both of which are key features of the human disease. In mice modeling Huntington's disease, JM6 prevented brain inflammation and the loss of synaptic connections between brain cells, while also extending lifespan.

“This discovery has significant implications for two devastating diseases and suggests that the KMO enzyme is a good protein for us to target with medications in diverse neurodegenerative disorders,” said Lennart Mucke, MD, who oversees all neurological research at Gladstone and who won the prestigious Potamkin Prize last year for developing experimental strategies to make the brain more resistant to Alzheimer's. “With any luck, Dr. Muchowski and his colleagues could begin testing this drug in patients within the next two years.”

Remarkably, JM6 (see structure) does not penetrate into the brain, but works by inhibiting KMO in the blood. The blood cells then send a protective signal to the brain, to stabilize brain-cell function and prevent neurodegeneration. The fact that the compound does not pass the so-called blood-brain barrier will facilitate testing in patients, as JM6's potential impact could be confirmed with a simple blood test.

JM6 was named for Dr. Muchowski's father, Dr. Joseph Muchowski, PhD, a retired medicinal chemist who helped his son devise the novel KMO inhibitor. The study was carried out in collaboration with the laboratories of Dr. Robert Schwarcz, a University of Maryland School of Medicine professor who pioneered studies linking KMO and metabolically related enzymes to nerve-cell loss, and Professor Eliezer Masliah at the University of California, San Diego, an expert in neuropathology.

 Ref : www.cell.com/abstract/S0092-8674(11)00581-2

Positive Results of Diltiazem from Fissure Trial

Ventrus Biosciences Inc. reported positive results from its Phase 3, randomized, double-blind, placebo-controlled clinical trial of diltiazem hydrochloride cream (VEN 307) in patients with anal fissures.

Ventrus' development partner, S.L.A. Pharma, has completed most of the outputs for the statistical analysis plan of the Phase 3 trial, and Ventrus is pleased to communicate the data that they have generated.

The Phase 3 study randomized 465 subjects to diltiazem hydrochloride 4% or 2% w/w cream, or placebo, applied topically three times daily (TID) for 8 weeks, followed by a 4 week blinded observation period. Both 4% and 2% diltiazem treatment arms demonstrated significant improvements compared to placebo in the primary endpoint of average of worst anal pain associated with or following defecation (pain score improvement 0.44, p=0.0108, 4%; 0.43, p=0.0134, 2%) and in the secondary endpoints of overall anal-fissure-related pain (pain score 0.36, p=0.030, 4%; 0.40, p=0.0183, 2%) and anal fissure healing (32.7%, p=0.0181, 4%; 31.2%, p=0.0359, 2%). Pain endpoints were assessed using an 11-point numerical pain rating scale (Likert-like scale).

Adverse events (AEs) were similar for the three treatment arms. Gastrointestinal Disorders were the most common. Reports of headaches were similar in the three arms (14.7% of 4% diltiazem, 12.3% of 2% diltiazem, and 14.2% of placebo). There was one serious adverse event of surgery for hemorrhoid reported in this trial. The study was conducted in 31 centers in Europe by S.L.A. Pharma, the product candidate's licensor. Ventrus holds rights to diltiazem hydrochloride cream in North America.

Based on these results, Ventrus will request a meeting with the U.S. Food and Drug Administration (FDA) to discuss the Phase 3 diltiazem study, as well as steps to move forward toward a New Drug Application (NDA). Because diltiazem is approved in oral formulations for the treatment of angina and high blood pressure, it is eligible for the FDA's 505(b)2 registration pathway. The Company is also preparing to initiate a second pivotal Phase 3 study of VEN 307 in anal fissures in the second half of 2012.

Ref : http://investor.ventrusbio.com/releasedetail.cfm?ReleaseID=672924

Trial will evaluate resveratrol in Alzheimer's dementia

In continuation of my update on Resveratrol

Researchers at Georgetown University and 25 other U.S. academic institutions affiliated with the Alzheimer's Disease Cooperative Study will be conducting a phase II double-blinded, placebo-controlled trial that will test the effects of resveratrol in Alzheimer's disease patients. "This is the gold-standard for conducting a clinical study because it allows us to objectively determine if resveratrol is offering any benefits," stated Brigid Reynolds, NP, who is the lead researcher for the study's center at Georgetown.

The twelve-month trial, funded by the National Institute on Aging, will enroll men and women age 50 and over with mild to moderate dementia diagnosed as probable Alzheimer's disease and will require one caregiver or friend for each patient. Participants will be initially assigned to 500 milligrams resveratrol or a placebo daily, with dosage to be increased at 13 week intervals to a maximum of 1,000 milligrams twice per day. Lumbar punctures, brain magnetic resonance imaging (MRI) scans, and blood and urine tests will monitor the subjects' progress over the course of ten visits. The researchers hope to determine whether supplementation with resveratrol is helpful in delaying or altering the deterioration of memory and daily function that occurs in Alzheimer's disease.

"Most resveratrol studies showing any health benefits have been conducted in animal models, such as mice, and with doses that far exceed intake from sipping wine or nibbling on chocolate," stated R. Scott Turner, MD, PhD, who is the director of Georgetown University Medical Center's Memory Disorders Program and the national study's lead investigator. "With this clinical trial, we'll find out if daily doses of pure resveratrol can delay or alter memory deterioration and daily functioning in people with mild to moderate dementia due to Alzheimer's."

"During this study, we will also test whether resveratrol improves glucose and insulin metabolism in older individuals -- although those who already have diabetes will not be included in this study," he added....

Ref : http://explore.georgetown.edu/news/?ID=64145

Ebola, Marburg Virus Treatments Safe in Phase 1 Studies

In continuation of my update on antisense drugs and RNAi

AVI BioPharma Inc. announced positive safety results from the first five cohorts of Phase 1 single ascending dose trials of AVI-6002 and AVI-6003, AVI's lead drug candidates being evaluated for the treatment of the Ebola virus and Marburg virus.

Data were evaluated by an independent Data and Safety Monitoring Board (DSMB), which issued recommendations for both studies to progress as planned to the next highest dosing level after no safety concerns were identified. The Phase 1 single ascending dose trials are designed to characterize the safety, tolerability, and pharmacokinetics of each therapeutic candidate in healthy adult volunteers.

"We are very encouraged that these two drugs, which use our advanced PMOplus chemistry, have demonstrated a favorable safety profile through five cohorts in our dose-escalation studies,”says Chris Garabedian, president and chief executive officer of AVI BioPharma...

Ref : http://phx.corporate-ir.net/phoenix.zhtml?c=64231&p=RssLanding&cat=news&id=1619940

To date, 25 healthy human subjects (five per group) have been enrolled into five sequential dose groups in each of the two studies. Within each group, four subjects received the indicated dose of the therapeutic and one subject received placebo. For each group, safety, clinical laboratory and renal biomarker results through five days after treatment were reviewed by a DSMB. Subjects enrolled in the sixth group for the drug studies will receive 9.0 mg/kg of the therapeutic or placebo. Final, un-blinded safety and pharmacokinetic results for all subjects will be available upon completion of the trial.

Both candidates employ AVI's patented PMOplus technology that selectively introduces positive charges to its phosphorodiamidate morpholino oligomer (PMO) backbone to improve interaction between the drug and its target.

Tivozanib Improves RCC (renal cell carinomas) Survival

Tivozanib (see structure, AV-951) is an oral VEGF receptor tyrosine kinase inhibitor. It is undergoing clinical trial investigation for the treatment of renal cell carinomas. An oral quinoline urea derivative, tivozanib suppresses angiogenesis by being selectively inhibitory against vascular endothelial growth factor.

The positive results of this Phase 2 trial informed the design and implementation of TIVO-1, a pivotal Phase 3 clinical study in advanced RCC demonstrating tivozanib superiority over sorafenib in the primary endpoint of PFS in the first-line setting, top-line data from which were reported in January 2012.

“Current RCC therapies are associated with toxicities that can interfere with patients’ treatment regimens and impact treatment efficacy and activities of daily living,” said Dmitry A. Nosov, M.D., Ph.D., senior clinical researcher at the Blokhin Oncology Research Center, Moscow, Russian Federation, lead author of the Phase 2 study and TIVO-1 investigator.

“Despite recent progress in treating patients with RCC, patients and physicians would benefit from a new RCC treatment option that delivers both improved efficacy and a more tolerable safety profile. The combined tivozanib efficacy and safety data demonstrated in this Phase 2 study supports tivozanib as a potential advancement in the RCC treatment landscape.”

Based on the positive Phase 2 data and success of the TIVO-1 trial, AVEO and its collaborator Astellas Pharma Inc. are moving forward with plans for submitting the tivozanib NDA in RCC in the third quarter of 2012, with the MAA submission to follow.

“We believe that the efficacy and safety profile consistently demonstrated by tivozanib and recently validated in our Phase 3 TIVO-1 trial represent an important step forward in the treatment of patients who have advanced RCC,” said William Slichenmyer, M.D., Sc.M., chief medical officer, AVEO. “We are pleased with the opportunity to collaborate with tivozanib study investigators on publishing these positive Phase 2 data in the Journal of Clinical Oncology, and look forward to advancing our work with our global partners at Astellas to bring tivozanib to patients who can benefit from this therapy.”....

http://jco.ascopubs.org/content/30/14/1678.abstract?sid=1fe73024-e1cc-481f-acc3-1dc09b596f7f